Methods and materials for treating nerve injuries and neurological disorders

ABSTRACT

This document provides methods and materials for treating nerve injuries and/or neurological disorders. For example, compositions including an amnion tissue preparation and/or a stem cell preparation as well as methods for using such compositions to treat a nerve injuries and/or neurological disorders are provided.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/567,160, filed Oct. 17, 2017, which is a National Stage Applicationof PCT/US17/16225, filed Feb. 2, 2017, which claims the benefit of U.S.Provisional Application No. 62/292,009, filed Feb. 5, 2016, and U.S.Provisional Application No. 62/293,866, filed Feb. 11, 2016, the contentof which Applications are incorporated herein by reference in theirentirety.

BACKGROUND 1. Technical Field

This document relates to methods and materials for treating nerveinjuries and/or neurological disorders. For example, this documentprovides methods and materials for using compositions (e.g., injectableformulations) that include an amnion tissue preparation and/or a stemcell preparation to treat nerve injuries and/or neurological disorders.

2. Background Information

Nerves are fragile and can be damaged by pressure, stretching, orcutting. Injury to a nerve can stop signals to and from the brain,causing muscles not to work properly, and a loss of feeling in theinjured area. In addition, hundreds of millions of people worldwide areaffected by neurological disorders. Approximately 6.2 million people diebecause of stroke each year. It is estimated that there are globally35.6 million people with dementia with 7.7 million new cases every year.

SUMMARY

This document provides compositions that include an amnion tissuepreparation and/or a stem cell preparation. Such compositions can beformulated for injection and used to treat nerve injuries (e.g., spinalcord injury) and/or neurological disorders (e.g., brain trauma, stroke,or dementia). This document also provides methods for using an amniontissue preparation, a stem cell preparation, or both in combination totreat nerve injuries (e.g., spinal cord injury) and/or neurologicaldisorders (e.g., brain trauma, stroke, or dementia).

In general, one aspect of this document features a method of treating anerve injury or a neurological disorder in a mammal. The methodcomprises, or consists essentially of, administering, to the mammal, anamnion tissue preparation lacking viable cells and a stem cellpreparation having viable cells, wherein a symptom of the a nerve injuryor neurological disorder is improved. The mammal can be a human, dog, orhorse. The method can comprise treating the nerve injury, and the nerveinjury is a spinal cord injury or a peripheral nerve injury. The methodcan comprise treating the nerve injury, and the nerve injury is apartially or fully severed nerve. The method can comprise treating theneurological disorder, and the neurological disorder is selected fromthe group consisting brain trauma, stroke, and dementia. The amniontissue preparation can be administered by injection into a neurologicaltissue of the mammal. The stem cell preparation can be administered byinjection into a neurological tissue of the mammal. The method canfurther comprise monitoring the nerve injury or neurological disorder ofthe mammal. The amnion tissue preparation can comprise an amnion tissuepreparation prepared from about 1 mg to about 10 g of amnion tissue perkg of body weight of the mammal. The stem cell preparation can comprisefrom about 0.3 million to about 3 million stem cells per kg of bodyweight of the mammal. The amnion tissue preparation can be a humanamnion tissue preparation. The stem cell preparation can be a humanmesenchymal stem cell preparation. The stem cell preparation. can be ahuman neural stem cell preparation.

In another aspect, this document features a composition comprising ablood vessel conduit, a stem cell preparation having viable cells, andan amnion tissue preparation. The blood vessel conduit can be a vein.The blood vessel conduit can be an artery. The amnion tissue preparationcan comprise viable cells. The amnion tissue preparation can lack viablecells. The stem cell preparation can be a human mesenchymal stem cellpreparation. The stem cell preparation can be a human neural stem cellpreparation. The composition can further comprise a therapeutic agent,an immunosuppressant agent, or a pharmaceutical excipient. Thecomposition can comprise from about 5 mg and about 5 g of the amniontissue preparation. The composition can comprise from about 10 mg andabout 1 g of the amnion tissue preparation. The stem cell preparation.can comprise from about 10 million to about 100 million stem cells.

In another aspect, this document features a nerve scaffold comprising acomposition comprising a stem cell preparation having viable cells andan amnion tissue preparation. The nerve scaffold can comprise a bloodvessel. The blood vessel can be a vein. The blood vessel can be anartery. The amnion tissue preparation can comprise viable cells. Theamnion tissue preparation can lack viable cells. The stem cellpreparation can be a human mesenchymal stem cell preparation. The stemcell preparation can be a human neural stem cell preparation. The nervescaffold can further comprise a therapeutic agent, an immunosuppressantagent, or a pharmaceutical excipient. The composition can comprise fromabout 5 mg and about 5 g of the amnion tissue preparation. Thecomposition can comprise from about 10 mg and about 1 g of the amniontissue preparation. The stem cell preparation can comprise from about 10million to about 100 million stem cells.

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention pertains. Although methods and materialssimilar or equivalent to those described herein can be used to practicethe invention, suitable methods and materials are described below. Allpublications, patent applications, patents, and other referencesmentioned herein are incorporated by reference in their entirety. Incase of conflict, the present specification, including definitions, willcontrol. In addition, the materials, methods, and examples areillustrative only and not intended to be limiting.

The details of one or more embodiments of the invention are set forth inthe accompanying drawings and the description below. Other features,objects, and advantages of the invention will be apparent from thedescription and drawings, and from the claims. The word “comprising” inthe claims may be replaced by “consisting essentially of” or with“consisting of,” according to standard practice in patent law.

DETAILED DESCRIPTION

This document provides methods and materials for treating nerve injuries(e.g., spinal cord injury) and/or neurological disorders (e.g., braintrauma, stroke, or dementia) using compositions that include an amniontissue preparation (e.g., human amnion tissue preparation) and/or a stemcell preparation (e.g., a human stem cell preparation).

A nerve injury and/or neurological disorder can affect the centralnervous system or the peripheral nervous system. The term “nerve injury”as used herein refers to any damage (e.g., crush, contusion, stretch,laceration, or severing) to a nervous tissue (e.g., nerve cells orneuroglia) causing an interruption in conduction of the impulse down thenerve fiber. Nerve injuries can include, without limitation, a spinalcord injury, a peripheral nerve injury, and a traumatic brain injury.The term “neurological disorder” as used herein refers to any conditionthat affects (e.g., directly or indirectly) the function of the nervoussystem. Neurological disorders can include, without limitation, braintrauma, stroke (e.g., ischemic stroke or hemorrhagic stroke), anddementia (e.g., Alzheimer's disease, vascular dementia, Lewy bodydementia, or frontotemporal dementia).

The term “amnion tissue preparation” as used herein refers to apreparation of amnion tissue or amnion material. In some cases, anamnion tissue preparation can be a liquid preparation (e.g., solution orsuspension) that is prepared from a dried amnion tissue preparation. Theterm “dried amnion tissue preparation” as used herein refers to apreparation of amnion tissue or amnion material that is dried to have awater content that is less than about 8 percent (e.g., less than about 7percent, less than about is 6 percent, less than about 5 percent, lessthan about 4 percent, less than about 3 percent, less than about 2percent, or less than about 1 percent). In some cases, a dried amniontissue preparation can have a water content that is between about 0.1percent and about 8 percent (e.g., between about 0.5 percent and about 8percent, between about 1 percent and about 8 percent, between about 0.1percent and about 5 percent, between about 0.1 percent and about 4percent, between about 0.1 percent and about 3 percent, between about0.5 percent and about 5 percent, or between about 1 percent and about 4percent). An amnion tissue preparation can be dried using anyappropriate technique such as micronization, vacuum drying, spraydrying, freeze drying, or combinations thereof. In some cases, an amniontissue preparation can be dried as described elsewhere (e.g., U.S. Pat.No. 5,656,498).

A dried amnion tissue preparation can have any appropriate particlesize. For example, a dried amnion tissue preparation can have a particlesize ranging from about 0.1 μm to about 25 μm (e.g., from about 0.5 μmto about 25 μm, from about 0.75 μm to about 25 μm, from about 1 μm toabout 25 μm, from about 0.1 μm to about 15 μm, from about 0.1 μm toabout 10 μm, from about 0.1 μm to about 7.5 μm, from about 0.1 μm toabout 5 μm, from about 0.75 μm to about 7.5 μm, or from about 1 μm toabout 5 μm).

An amnion tissue preparation or a dried amnion tissue preparation cancontain viable cells, non-viable cells, or a combination thereof. Forexample, an amnion tissue preparation or a dried amnion tissuepreparation can be a preparation of amnion tissue or amnion materialhaving viable cells. In some cases, an amnion tissue, preparation can bea solution or suspension of amnion tissue or amnion material havingviable cells.

In some cases, an amnion tissue preparation or a dried amnion tissuepreparation can be a preparation of amnion tissue or amnion materialwhere all the cells were removed, killed, or lysed such that the amniontissue preparation or the dried amnion tissue preparation lacks viablecells. In some cases, an amnion tissue preparation or a dried amniontissue preparation can be a preparation of amnion tissue o or amnionmaterial that was exposed to one or more physical and/or chemicaltreatments that killed, fixed, or lysed the cells of the amnion tissueor amnion material such that the amnion tissue preparation or the driedamnion tissue preparation lacks viable cells. For example, temperature(e.g., rapid freezing or rapid freezing-thawing), force and pressure,and/or electrical disruption can be used to kill or lyse is cells withinamnion tissue or amnion material to produce an amnion tissue preparationor a dried amnion tissue preparation that lacks viable cells.

In some cases, amnion tissue or amnion material can be obtained and thentreated in a manner designed to lyse all the cells within the amniontissue or amnion material. In these cases, the resulting material (e.g.,matrix material and cellular remnants from lysed cells) can be used asan amnion tissue preparation that lacks viable cells or dried to form adried amnion tissue preparation that lacks viable cells.

In some cases, an amnion tissue preparation or a dried amnion tissuepreparation can be prepared from human amnion tissue. For example, humanamnion tissue can be harvested, processed to maintain cell viabilitywith or without removing blood, and used as an amnion tissue preparationor dried to form a dried amnion tissue preparation.

In some cases, human amnion tissue can be processed to remove bloodprior to being used as an amnion tissue preparation or prior to beingdried to form a dried amnion tissue preparation. In some cases, humanamnion tissue can be processed without removing cells or blood prior toforming an amnion tissue preparation or a dried amnion tissuepreparation.

An example of an amnion tissue preparation includes, without limitation,a human amnion tissue preparation that includes viable cells. In somecases, an amnion tissue preparation can be obtained from MiMedX® or atissue bank (e.g., a human tissue bank).

The term “stem cell preparation” as used herein refers to a preparationof stem cells or stem cell material. In some cases, a stem cellpreparation can be a liquid preparation (e.g., solution or suspension).

A stem cell preparation can contain viable stem cells, non-viable stemcells, or a combination thereof. For example, a stem cell preparationcan be a preparation of viable stem cells. In some cases, a stem cellpreparation can be a solution or suspension of viable stem cells.

In some cases, a stem cell preparation can be a preparation of stem cellor stem cell material where all the stem cells were killed, fixed, orlysed such that the stem cell preparation lacks viable stem cells. Insome cases, a stem cell preparation can be a preparation of stem cellsor stem cell material that was exposed to one or more physical and/orchemical treatments that killed, fixed, or lysed the stem cells suchthat the stem cell preparation lacks viable stem cells. For example,temperature (e.g., rapid freezing or rapid freezing-thawing), force andpressure, and/or electrical disruption can be used to kill or lyse stemcells to produce a stem cell preparation that lacks viable stem cells.

In some cases, a stem cell culture can be obtained and then used as astem cell preparation in a manner that maintains stem cell viability.

Examples of stem cell preparations include, without limitation, amesenchymal stem cell (MSC) preparation (e.g., a MSC preparationobtained from fat tissue or bone marrow), a neural stem cell (NSC)preparation (e.g., a NSC preparation obtained from a brain tissue suchas striatum), an umbilical cord blood stem cell preparation, anembryonic stem cell preparation, and a human induced pluripotent stemcell preparation.

In some cases, stem cell preparations are prepared from cultures of stemcells. For example, a culture containing from about 25 million to about25 billion stem cells can be used to make a stem cell preparation. Insome cases, from about 0.1 million to about 3 million (e.g., from about0.3 million to about 3 million, from about 0.5 million to about 3million, from about 0.75 million to about 3 million, from about 1million to about 3 million, from about 1.5 million to about 3 million,from about 0.3 million to about 2.5 million, from about 0.3 million toabout 2.0 million, from about 0.3 million to about 1.5 million, fromabout 0.3 million to about 1.0 million, from about 0.5 million to about2.5 million, from about 0.75 million to about 2.0 million, from about0.8 million to about 1.5 million) stem cells per kg of body weight of amammal (e.g., a human) to be treated can be used to make a stem cellpreparation for administration to that mammal. In some cases, a stemcell preparation can include from about 0.025 million to about 12million from about 2 million to about 6 million) stem cells per kg ofbody weight of a mammal intended to receive the stem cell preparation.For example, when administering a stem cell preparation to a ratweighing about 250 g, a stem cell preparation can include between about0.75 million and 1.25 million stem cells. The volume of such anadministration can be from about 45 μL to about 65 μL (e.g., about 50-60μL). These amounts and volumes can be increased appropriately for largermammals (e.g., cats, dogs, horses, or humans). In some cases, a stemcell preparation and an amnion tissue preparation can be formulated intoa single solution or suspension for administration to a mammal. Forexample, a dried amnion tissue preparation can be reconstituted into asolution and a is stem cell preparation can be added to that solution toform a single solution or suspension having both a stem cell preparationand an amnion tissue preparation. In some cases, a stem cell preparationcan be obtained commercially from a variety of suppliers such asStemedica Cell Technologies, Inc.

Typically, a composition described herein (e.g., a compositioncontaining an amnion tissue preparation lacking viable cells and a stemcell preparation having viable stem cells or a composition containing anamnion tissue preparation having viable cells, a stem cell preparationhaving viable stem cells, or both an amnion tissue preparation havingviable cells and a stem cell preparation having viable stem cells) isadministered via injection or infusion. For example, a compositioncontaining an amnion tissue preparation lacking viable cells (e.g., adried amnion tissue preparation) and a stem cell preparation havingviable stem cells can be injected intravenously and/or into or near thesite of a nerve injury and/or into a neurological tissue of a mammalhaving a neurological disorder. In some cases, a composition containingan amnion tissue preparation having viable cells and a stem cellpreparation having viable stem cells can be injected into or near thesite of nerve injury and/or into a neurological tissue of a mammalhaving a neurological disorder. In some cases, a composition describedherein (e.g., a composition containing an amnion tissue preparationlacking viable cells and a stem cell preparation having viable stemcells or a composition containing an amnion tissue preparation havingviable cells, a stem cell preparation having viable stem cells, or bothan amnion tissue preparation having viable cells and a stem cellpreparation having viable stem cells) is administered during aneurosurgical procedure.

In some cases, a composition that includes an amnion tissue preparation(e.g., an amnion tissue preparation having viable cells or an amniontissue preparation lacking viable cells) and/or a stem cell preparation(e.g., a stem cell preparation having viable stem cells) is included ina nerve scaffold (e.g., a nerve graft or a nerve conduit). For example,a nerve scaffold including a composition containing an amnion tissuepreparation lacking viable cells (e.g., a dried amnion tissuepreparation) and a stem cell preparation having viable stem cells can beimplanted into a mammal having a nerve injury and/or a neurologicaldisorder. A nerve scaffold can include biological materials (e.g., bloodvessels (e.g., veins, arteries, or capillaries) or skeletal muscles) orsynthetic materials (e.g., silicones or polyglycolides). In some cases,a nerve scaffold including a composition containing an amnion tissuepreparation having viable cells and a stem cell preparation havingviable stem cells can be implanted into a mammal having a nerve injuryand/or a neurological disorder. In some cases, a nerve scaffoldincluding a composition described herein (e.g., composition containingan amnion tissue preparation lacking viable cells and a stem cellpreparation having viable stem cells or a composition containing anamnion tissue preparation having viable cells, a stem cell preparationhaving viable stem cells, or both an amnion tissue preparation havingviable cells and a stem cell preparation having viable stem cells) isimplanted during a neurosurgical procedure.

In some cases, a composition that includes an amnion tissue preparation(e.g., an amnion tissue preparation having viable cells or an amniontissue preparation lacking viable cells) and/or a stem cell preparation(e.g., a stem cell preparation having viable stem cells) also caninclude one or more therapeutic agents, one or more immunosuppressantagents (e.g., corticosteroids (e.g., glucocorticoids), cytostatics,antibodies, calcineurin inhibitors, and interferons), one or moreanti-inflammatory agents (e.g., non-steroidal anti-inflammatory drugs,dexamethasone or other type of glucocorticoid steroids), one or moregrowth factors (e.g., platelet derived growth factor PDGF, epithelialgrowth factor (EGF), fibroblast growth factor-2 (FGF2), or stem cellfactor (SCF)), and/or one or more antimicrobial agents (e.g.,antibiotics such kanamycin, neomycin, streptomycin, or gentamicin, or anantifungal agent).

As described herein, nerve injuries and/or neurological disorders can betreated by administering (e.g., via injection such as an intravenousinjection or an injection into an neurological tissue) an effectiveamount of a composition that includes an amnion tissue preparationdescribed herein (e.g., an amnion tissue preparation having viable cellsor an amnion tissue preparation lacking viable cells), and/or a stemcell preparation described herein (e.g., a stem cell preparation havingviable stem cells). For example, compositions described herein can beused to treat a subject having a nerve injury and/or a neurologicaldisorder, or at risk of developing a neurological disorder. In somecases, a composition can include an amnion tissue preparation (e.g., anamnion tissue preparation having viable cells or an amnion tissuepreparation lacking viable cells), a NSC preparation (e.g., a stem cellpreparation having viable stem cells), and one or more immunosuppressantagents (e.g., a corticosteroid). Effective amounts of compositionsdescribed herein can be determined by a physician, taking into accountvarious factors such as overall health is status, body weight, sex,diet, time and route of administration, other medications, and any otherrelevant clinical factors. As used herein, an “effective amount” or“therapeutically effective amount” of a composition provided herein isthe amount that is sufficient to provide a beneficial effect to thesubject to which the composition or preparations are delivered. Theeffective amount can be the amount effective to achieve a more rapidrecovery, an improvement in the quality of life, or an improvement orelimination of one or more symptoms (e.g., paralysis, muscle weakness,poor coordination, loss of sensation, loss of sight, loss of speech,seizures, confusion, memory loss (e.g., short-term memory loss orlong-term memory loss), pain, or altered levels of consciousnessassociated with a subject's nerve injury and/or neurological disorder.

In some embodiments, the methods include delivering, to the subject, anamnion tissue preparation (e.g., an amnion tissue preparation havingviable cells or an amnion tissue preparation lacking viable cells) madewith from about 0.01 mg to about 10 g (e.g., from about 0.01 mg to about10 g, from about 0.1 mg to about 10 g, from about 1 mg to about 10 g,from about 10 mg to about 10 g, from about 100 mg to about 10 g, fromabout 1 g to about 10 g, from about 0.01 mg to about 5 g, from about0.01 mg to about 1 g, from about 0.01 mg to about 100 mg, from about 10mg to about 5 g, from about 100 mg to about 1 g, or from about 1 g toabout 5 g) of amnion tissue per kg body weight of the subject beingtreated.

In some embodiments, the methods include delivering, to the subject, astem cell preparation (e.g., a stem cell preparation having viable stemcells) made from about 0.1 million to about 3 million (e.g., from about0.3 million to about 3 million, from about 0.5 million to about 3million, from about 0.75 million to about 3 million, from about 1million to about 3 million, from about 1.5 million to about 3 million,from about 0.3 million to about 2.5 million, from about 0.3 million toabout 2.0 million, from about 0.3 million to about 1.5 million, fromabout 0.3 million to about 1.0 million, from about 0.5 million to about2.5 million, from about 0.75 million to about 2.0 million, from about0.8 million to about 1.5 million) stem cells per kg body weight of thesubject being treated. In some cases, a stem cell preparation caninclude from about 0.025 million to about 12 million (e.g., from about 2million to about 6 million) stem cells per kg of body weight of a mammalintended to receive the stem cell preparation. For example, whenadministering a stem cell preparation to a rat weighing about 250 g, astem cell preparation can include between about 0.75 million and 1.25million stem cells. The volume of such an administration can be fromabout 45 μL to about 65 μL (e.g., about 50-60 μL). These amounts andvolumes can be increased appropriately for larger mammals (e.g., cats,dogs, horses, or humans).

In some embodiments, a composition containing an amnion tissuepreparation (e.g., an amnion tissue preparation having viable cells oran amnion tissue preparation lacking viable cells) and/or a stem cellpreparation (e.g., a stem cell preparation having viable stem cells) isdelivered to the subject (e.g., by injection) only once. In someembodiments, multiple (e.g., two, three, four, five, six, seven, eight,nine, 10, 11, 12, 13, 14, 15, or 20 or more) administrations can beused. For example, multiple deliveries of a composition containing anamnion tissue preparation (e.g., an amnion tissue preparation havingviable cells or an amnion tissue preparation lacking viable cells)and/or a stem cell preparation (e.g., a stem cell preparation havingviable stem cells) can be made over the course of several (e.g., two,three, four, five, six, seven, eight, nine, 10, 14, 21, 28, or 31 ormore) consecutive days (e.g., one delivery each day for seven days orone delivery every other day for seven days). In some cases, acomposition containing an amnion tissue preparation (e.g., an amniontissue preparation having viable cells or an amnion tissue preparationlacking viable cells) and/or a stem cell preparation (e.g., a stem cellpreparation having viable stem cells) can be delivered from about once aweek to about once per year (e.g., once every month or once every othermonth). In some cases, a composition containing an amnion tissuepreparation (e.g., an amnion tissue preparation having viable cells oran amnion tissue preparation lacking viable cells) and/or a stem cellpreparation (e.g., a stem cell preparation having viable stem cells) canbe delivered to a subject for several months (e.g., one delivery permonth for six months, or one delivery per week for two months).

A composition containing an amnion tissue preparation (e.g., an amniontissue preparation having viable cells or an amnion tissue preparationlacking viable cells) and/or a stem cell preparation (e.g., a stem cellpreparation having viable stem cells) can be delivered to a subject atvarious time points after diagnosis with a nerve injury and/or aneurological disorder. For example, a composition containing an amniontissue preparation (e.g., an amnion tissue preparation having viablecells or an amnion tissue preparation lacking viable cells) and/or astem cell preparation (e.g., a stem cell preparation having viable stemcells) can be delivered immediately following diagnosis with a nerveinjury and/or a neurological disorder. In some cases, a compositioncontaining an amnion tissue preparation (e.g., an amnion tissuepreparation having viable cells or an amnion tissue preparation lackingviable cells) and/or a stem cell preparation (e.g., a stem cellpreparation having viable stem cells) can be delivered to a subject lessthan 10 (e.g., 9, 8, 7, 6, 5, 4, 3, 2, or 1) days after diagnosis with anerve injury and/or a neurological disorder.

The subject treated as described herein can be any mammal, a human(e.g., a human patient) or a non-human primate (e.g., chimpanzee,baboon, or monkey), a mouse, a rat, a rabbit, a guinea pie, a gerbil, ahamster, a horse, a camel, a type of livestock (e.g., cow, pig, sheep,or goat), a mammalian zoo animal (e.g., a lion, a tiger, or a leopard),a dog, or a cat.

A composition containing an amnion tissue preparation (e.g., an amniontissue preparation having viable cells or an amnion tissue preparationlacking viable cells) and/or a stem cell preparation (e.g., a stem cellpreparation having viable stem cells) can be administered to a subjectas a combination therapy with another treatment used to treat a nerveinjury and/or a neurological disorder. For example, a combinationtherapy can include administering to the subject (e.g., a human patient)one or more additional agents that provide a therapeutic benefit to thesubject who has a nerve injury and/or neurological disorder, or is atrisk of developing a neurological disorder. In some cases, thecomposition and the one or more additional agents can be administered atthe same time. In some cases, the composition can be administered first,and the one or more additional agents administered second, or viceversa.

The efficacy of a given treatment in treating a nerve injury and/or aneurological disorder can be defined as an improvement of one or moresymptoms of the nerve injury and/or the neurological disorder by atleast 5% (e.g., at least 10%, at least 15%, at least 20%, at least 25%,at least 30%, at least 40%, at least 50%, at least 55%, at least 60%, atleast 65% or more). In some cases, efficacy of a treatment with acomposition containing an amnion tissue preparation (e.g., an amniontissue preparation having viable cells or an amnion tissue preparationlacking viable cells) and/or a stem cell preparation (e.g., a stem cellpreparation having viable stem cells) can be determined from thestabilization of one or more symptoms associated with the nerve injuryand/or the neurological disorder (i.e., the treatments curtail theworsening of one or more symptoms of the nerve injury and/or theneurological disorder).

In some cases, the methods described herein can include monitoring anerve injury and/or a neurological disorder in the subject to, forexample, determine if the nerve injury and/or the neurological disorderis improving with treatment. Any appropriate method can be used tomonitor the nerve injury and/or the neurological disorder. For example,cognitive impairment can be monitored, physical impairment can bemonitored, pain can be monitored, medical imaging (e.g., neuroimagingusing computer assisted tomography (CAT scans), magnetic resonanceimaging (MRIs), and/or X-rays) can be performed.

A composition containing an amnion tissue preparation (e.g., an amniontissue preparation having viable cells or an amnion tissue preparationlacking viable cells) and/or a stem cell preparation (e.g., a stem cellpreparation having viable stem cells) can be combined with packagingmaterial and sold as a kit. The packaging material included in a kittypically contains instructions or a label describing how thecomposition can be administered via, for example, injection such as anintravenous injection or an injection into or near one or moreneurological tissues (e.g., brain, spinal cord, cranial nerves,peripheral nerves, nerve roots, and/or neuromuscular junctions). A kitalso can include a unit dose injector. The term “unit dose injector”refers to an injection device that delivers a single dose of acomposition containing an amnion tissue preparation (e.g., an amniontissue preparation having viable cells or an amnion tissue preparationlacking viable cells) and/or a stem cell preparation (e.g., a stem cellpreparation having viable stem cells) by injection into a user.Typically, a unit dose injector contains a single container that holdsor contains an injectable formulation.

OTHER EMBODIMENTS

It is to be understood that while the invention has been described inconjunction with the detailed description thereof, the foregoingdescription is intended to illustrate and not limit the scope of theinvention, which is defined by the scope of the appended claims. Otheraspects, advantages, and modifications are within the scope of thefollowing claims.

1. A nerve scaffold comprising: a blood vessel conduit selected from avein or an artery; a composition comprising a stem cell preparationhaving viable cells and an amnion tissue preparation, wherein the amniontissue preparation is a reconstituted amnion tissue preparation; andwherein the blood vessel conduit is bathed in the composition.
 2. Thenerve scaffold of claim 1, wherein the reconstituted amnion tissuepreparation is a dried reconstituted amnion tissue preparation.
 3. Thenerve scaffold of claim 2, wherein the dried reconstituted amnion tissuepreparation has a water content of less than about 8 percent.
 4. Thenerve scaffold of claim 2, wherein the dried reconstituted amnion tissuepreparation has a particles size of from about 0.1 um to about 25 um. 5.The nerve scaffold of claim 1, wherein the amnion tissue preparation isa solution comprising amnion tissue and viable cells.
 6. The nervescaffold of claim 1, wherein the amnion tissue preparation a suspensioncomprising amnion tissue and viable cells.
 7. The nerve scaffold ofclaim 1, wherein the amnion tissue preparation comprises non-viablecells.
 8. The nerve scaffold of claim 1, wherein the reconstitutedamnion tissue preparation comprises from about 1 mg to about 10 g ofamnion tissue per kg of body weight of a recipient mammal.
 9. The nervescaffold of claim 1, wherein the composition further comprises atherapeutic agent, an immunosuppressant agent, or a pharmaceuticalexcipient.
 10. The nerve scaffold of claim 1, wherein the compositioncomprises from about 5 mg and about 5 g of the reconstituted amniontissue preparation.
 11. The nerve scaffold of claim 1, wherein thereconstituted amnion tissue preparation is void of blood.
 12. The nervescaffold of claim 1, wherein the reconstituted amnion tissue preparationcomprises blood and cells.
 13. The nerve scaffold of claim 1, whereinthe stem cell preparation is a liquid preparation.
 14. The nervescaffold of claim 1, wherein the amnion tissue preparation comprisesfrom about 0.025 million to about 12 million stem cells per kilogram ofbody weight of a mammal.
 15. An injector device for treating a nerveinjury or a neurological disorder in a mammal, the injector devicecomprising: a container comprising a composition comprising a stem cellpreparation having viable cells and an amnion tissue preparation whereinthe amnion tissue preparation lacks viable cells; and an injectorcapable of administering a single dose of the composition.
 16. Theinjector device of claim 15, wherein the amnion tissue preparation is areconstituted amnion tissue preparation.
 17. The injector device ofclaim 15, wherein the amnion tissue preparation is a dried reconstitutedamnion tissue preparation.
 18. The injector device of claim 15, whereinthe amnion tissue preparation is a solution comprising amnion tissue andviable cells.
 19. The injector device of claim 15, wherein the amniontissue preparation is a suspension comprising amnion tissue and viablecells.
 20. The injector device of claim 15, wherein the amnion tissuepreparation comprises from about 1 mg to about 10 g of amnion tissue perkg of body weight of a recipient mammal.